1. Field
Example embodiments relate to a specific peptide binding to glypican-3 protein, and, more particularly, to a peptide which specifically binds to glypican-3 protein overexpressed in some malignant tumors and which may be used in diagnosis and treatment of a corresponding malignant disease while minimizing effects on other normal organs.
2. Description of the Related Art
Hepatocellular carcinoma (HCC) is usually asymptomatic at early stages and has a great propensity for intravascular or intrabiliary invasion, even when the primary tumor is small. As a result, HCC is generally at an advanced stage when discovered and only 10-20% of primary HCCs are found to be resectable at the time of diagnoses.
A molecular marker for screening and diagnosis of HCC is alphafetoprotein (AFP). Although alphafetoprotein occurs only during prenatal life in normal tissues, it is known to be an oncofetal protein due to its reactivated occurrence in many liver cancer cells. AFP concentration decreases gradually after birth to <10 ng/ml in 12-18 months. If AFP levels are 20 ng/ml or higher, 60 to 80% of HCC cases are detected, but sensitivity is significantly lower in the case of small tumors.
The size of a tumor is a significant risk factor for intrahepatic spread and metastasis of HCC. Many more treatment options are available for patients with small tumors while symptomatic tumors are generally large, and often beyond therapeutic intervention. Because the currently used serological test is a sequential AFP analysis which is low in sensitivity, it is difficult to detect tumors when they are small. Another problem with the use of AFP as a marker for HCC is its lack of specificity. Significant increases of AFP are seen in a considerable number of patients with chronic liver diseases. It has been reported that 15-58% of patients with chronic hepatitis, and 11-47% of patients with cirrhosis had increased serum AFP. It is, therefore, not uncommon that serum AFP levels in patients with HCC and cirrhosis overlap, which confounds the interpretation of the results of the AFP assay. In view of the unreliability of AFP levels, most screening regimens include ultrasonography, which is highly sensitive to liver tumors. However, ultrasonography lacks specificity, and cannot reliably distinguish between HCC, cirrhotic nodule, and dysplastic nodule when the lesions are smaller than about 2 cm.
Although there are a number of treatment methods, HCC has been known to be a difficult-to-treat carcinoma due to bad prognostic results compared to other carcinomas. When found in early stages, the carcinoma may be subjected to a surgical therapy for treatment. However, the carcinoma is rarely found in early stages and includes multiple extraheptic metastases, indicating that most surgeries may not be performed for treatment. Although the location and size of HCC is suitable for surgery, in most cases surgical options are not possible due to accompanying liver diseases. For these reasons, in HCC cases which prohibit surgical means, treatments such as transcatheter arterial embolization (TAE), transcatheter arterial chemoembolization (TACE), percutaneous ethanol injection (PEI), percutaneous radiofrequency therapy, and percutaneous radionuclide injection have been tried with limited effects. When treatment has been tried by systemically administering antitumor agents to a patient, partial effects may be obtained and symptoms may be aggravated by secondary side effects of chemotherapies. Thus, if a specific treatment method including binding to antigens specifically overexpressed in HCC were to be developed, it might be a treatment method which would effectively remove only carcinomas without harming other normal tissues. Furthermore, it may be a plausible treatment method for patients whose liver functions are so degraded that no other treatments may be used as well as for all the terminal stage patients.